scholarly journals Counter-Selection of Antimalarial Resistance Polymorphisms by Intermittent Preventive Treatment in Pregnancy

2019 ◽  
Author(s):  
Silvie Huijben ◽  
Eusebio Macete ◽  
Ghyslain Mombo-Ngoma ◽  
Michael Ramharter ◽  
Simon Kariuki ◽  
...  
Keyword(s):  
Pregnancy Outcomes ◽  
Copy Number ◽  
Intermittent Preventive Treatment ◽  
Preventive Treatment ◽  
Antimalarial Resistance ◽  
Resistance Markers ◽  
The Impact ◽  
Pfmdr1 Copy Number ◽  
Selection Of ◽  
In Pregnancy

Abstract Background Innovative approaches are needed to limit antimalarial resistance evolution. Understanding the role of intermittent preventive treatment in pregnancy (IPTp) on the selection for resistance and the impact such selection has on pregnancy outcomes can guide future interventions. Methods Plasmodium falciparum isolates (n = 914) from 2 randomized clinical trials were screened for pfmdr1 copy number variation and pfcrt, pfmdr1, pfdhfr, and pfdhps resistance markers. The trials were conducted between 2010 and 2013 in Benin, Gabon, Kenya, and Mozambique to establish the efficacy of IPTp-mefloquine (MQ) compared with IPTp-sulphadoxine-pyrimethamine (SP) in human immunodeficiency virus (HIV)-uninfected and to IPTp-placebo in HIV-infected women. Results In HIV-uninfected women, the prevalence of pfcrt mutants, pfdhfr/pfdhps quintuple mutants, and pfmdr1 copy number was similar between women receiving IPT-SP and IPTp-MQ. However, prevalence of pfmdr1 polymorphism 86Y was lower in the IPTp-MQ group than in the IPTp-SP group, and within the IPTp-MQ group it was lower at delivery compared with recruitment. No effect of IPTp-MQ on resistance markers was observed among HIV-infected women. The carriage of resistance markers was not associated with pregnancy outcomes. Conclusions Selection of wild-type pfmdr1 polymorphism N86 by IPTp-MQ highlights the strong selective pressure IPTp can exert and the opportunity for using negative cross-resistance in drug choice for clinical treatment and IPTp.

The impact of intermittent preventive treatment with sulfadoxine-pyrimethamine on the prevalence of malaria parasitaemia in pregnancy

2012 ◽  
Vol 42 (3) ◽  
pp. 133-135 ◽  
Author(s):  
Uchenna Anthony Umeh ◽  
Samuel N Obi ◽  
Hyacinth E Onah ◽  
Emmanuel Onyebuchi V Ugwu ◽  
Leonard Ogbonna Ajah ◽  
...  
Keyword(s):  
Intermittent Preventive Treatment ◽  
Preventive Treatment ◽  
Malaria Parasitaemia ◽  
The Impact ◽  
In Pregnancy

scholarly journals Intermittent Preventive Treatment with Dihydroartemisinin-Piperaquine in Ugandan Schoolchildren Selects for Plasmodium falciparum Transporter Polymorphisms That Modify Drug Sensitivity

2016 ◽  
Vol 60 (10) ◽  
pp. 5649-5654 ◽  
Author(s):  
Joaniter I. Nankabirwa ◽  
Melissa D. Conrad ◽  
Jennifer Legac ◽  
Stephen Tukwasibwe ◽  
Patrick Tumwebaze ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Drug Sensitivity ◽  
Selective Pressure ◽  
Intermittent Preventive Treatment ◽  
Preventive Treatment ◽  
Drug Pressure ◽  
Content Type ◽  
The Past ◽  
The Impact ◽  
Selection Of

ABSTRACTDihydroartemisinin-piperaquine (DP) offers prolonged protection against malaria, but its impact onPlasmodium falciparumdrug sensitivity is uncertain. In a trial of intermittent preventive treatment in schoolchildren in Tororo, Uganda, in 2011 to 2012, monthly DP for 1 year decreased the incidence of malaria by 96% compared to placebo; DP once per school term offered protection primarily during the first month after therapy. To assess the impact of DP on selection of drug resistance, we compared the prevalence of key polymorphisms in isolates that emerged at different intervals after treatment with DP. Blood obtained monthly and at each episode of fever was assessed forP. falciparumparasitemia by microscopy. Samples from 160 symptomatic and 650 asymptomatic episodes of parasitemia were assessed at 4 loci (N86Y, Y184F, and D1246Y inpfmdr1and K76T inpfcrt) that modulate sensitivity to aminoquinoline antimalarials, utilizing a ligase detection reaction-fluorescent microsphere assay. Forpfmdr1N86Y andpfcrtK76T, but not the other studied polymorphisms, the prevalences of mutant genotypes were significantly greater in children who had received DP within the past 30 days than in those not treated within 60 days (86Y, 18.0% versus 8.3% [P= 0.03]; 76T, 96.0% versus 86.1% [P= 0.05]), suggesting selective pressure of DP. Full sequencing ofpfcrtin a subset of samples did not identify additional polymorphisms selected by DP. In summary, parasites that emerged soon after treatment with DP were more likely than parasites not under drug pressure to harborpfmdr1andpfcrtpolymorphisms associated with decreased sensitivity to aminoquinoline antimalarials. (This study has been registered at ClinicalTrials.gov under no. NCT01231880.)

scholarly journals Sub-optimal Intermittent Preventive Treatment in pregnancy (IPTp) is associated with an increased risk of submicroscopic P. falciparum infection in pregnant women: a prospective cohort study in Benin

2020 ◽  
Author(s):  
Cornélia P A Hounkonnou ◽  
Nicaise Tuikue Ndam ◽  
Nadine Fievet ◽  
Manfred Accrombessi ◽  
Emmanuel Yovo ◽  
...  
Keyword(s):  
Gestational Age ◽  
Negative Binomial ◽  
Intermittent Preventive Treatment ◽  
Preventive Treatment ◽  
Malaria In Pregnancy ◽  
Sub Saharan Africa ◽  
Increased Risk ◽  
Sub Saharan ◽  
The Impact ◽  
In Pregnancy

Abstract Background Harmful maternal and neonatal health outcomes result from malaria in pregnancy, the prevention of which primarily relies on intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP). WHO recommends IPTp-SP in sub-Saharan Africa, but implementation is highly heterogeneous and often sub-optimal in terms of the number of doses and their timing. In this study, we assessed the impact of this heterogeneity on malaria in pregnancy, mainly with respect to submicroscopic Plasmodium falciparum infections. Methods We used data from 273 Beninese women followed throughout pregnancy. Screening for P. falciparum infections, using both microscopy- and polymerase chain reaction (PCR) -based methods, was performed monthly, and information on IPTp-SP dose was collected. Gestational age was estimated by repeated ultrasound scans. Using a negative binomial model, we investigated the effect of IPTp-SP doses and timing, after 17 weeks of gestation, on the number of P. falciparum infections, focusing on submicroscopic infections detectable only by PCR. Results At least two IPTp-SP doses were taken by 77.3% of the women. The median gestational age at first IPTp-SP dose was 22 weeks. A late first IPTp-SP dose (>21.2 weeks) was marginally associated with an increased number of P. falciparum infections (adjusted incidence rate ratio [aIRR] =1.3; p=0.098). The number of IPTp-SP doses was not associated with the number of submicroscopic infections (aIRR=1.2, p=0.543). Conclusion A late first IPTp-SP dose fail to provide optimal protection against P. falciparum, especially submicroscopic infections. This highlights the need for a new antimalarial drug for IPTp that could be taken early in pregnancy.

scholarly journals Intermittent Preventive Treatment of Malaria in Pregnancy: Assessment of the Sulfadoxine-Pyrimethamine Three-Dose Policy on Birth Outcomes in Rural Northern Ghana

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Francis Anto ◽  
Ibrahim Haruna Agongo ◽  
Victor Asoala ◽  
Elizabeth Awini ◽  
Abraham Rexford Oduro
Keyword(s):  
Birth Outcomes ◽  
Pregnancy Outcomes ◽  
Intermittent Preventive Treatment ◽  
Preventive Treatment ◽  
Normal Weight ◽  
Malaria In Pregnancy ◽  
Northern Ghana ◽  
Background Characteristics ◽  
Chi Square ◽  
In Pregnancy

Background. Intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) decreases placental parasitaemia and improves birth outcomes. Currently, WHO recommends three or more doses of SP given during antenatal care (ANC), spaced one month apart after 16 weeks of gestation till delivery. This study determined the level of uptake of SP and its association with birth outcomes in rural northern Ghana. Methods. A survey was carried out at the War Memorial Hospital in Navrongo, Ghana, among mothers who had delivered within ten weeks and were seeking postnatal care. Data on time of first ANC, number of visits, receipt of IPTp-SP, and birth outcomes were extracted from the antenatal records of 254 mothers. Mothers were interviewed on their background characteristics and obstetric history. Chi-square tests and logistic regression were carried out to determine association between antenatal indicators, uptake of IPTp-SP, and birth outcomes using Stata version 13. Results. Uptake of three-five doses of SP was IPT3 =76.4%, IPT4 =37.3%, and IPT5 = 16.0%. Receipt of first dose of SP at 16, 17-24, and 25-36 weeks of gestation was 16.9%, 56.7%, and 26.4%, respectively. Taking the first dose of SP during the second trimester allowed for taking ≥3 doses of SP compared to taking the first dose during the third trimester (χ2 = 60.1, p<0.001). Women who made ≥4 visits were more likely to receive ≥3 doses of SP compared to those who made <4 visits (χ2 = 87.6, p<0.001). Women who received ≥ 3 doses of SP were more likely (OR = 3.3; 95% CI: 1.69-6.33) to give birth at term and also have normal weight babies (OR =4.0; 95% CI: 1.98-8.06). Conclusion. Uptake of three or more doses of SP contributed to improved pregnancy outcomes. Increased efforts towards improving early ANC attendance could increase uptake of SP and improve pregnancy outcomes.

scholarly journals Coverage of intermittent preventive treatment of malaria in pregnancy in four sub-Saharan countries: findings from household surveys

2020 ◽  
Author(s):  
Clara Pons-Duran ◽  
Mireia Llach ◽  
Charfudin Sacoor ◽  
Sergi Sanz ◽  
Eusebio Macete ◽  
...  
Keyword(s):  
Antenatal Care ◽  
Intermittent Preventive Treatment ◽  
Preventive Treatment ◽  
Malaria Prevention ◽  
Reproductive Age ◽  
Cluster Sampling ◽  
Household Surveys ◽  
Cross Sectional ◽  
Sub Saharan ◽  
In Pregnancy

Abstract Background Intermittent preventive treatment in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) is a key malaria prevention strategy in areas with moderate to high transmission. As part of the TIPTOP (Transforming IPT for Optimal Pregnancy) project, baseline information about IPTp coverage was collected in eight districts from four sub-Saharan countries: Democratic Republic of Congo (DRC), Madagascar, Mozambique and Nigeria. Methods Cross-sectional household surveys were conducted using a multistage cluster sampling design to estimate the coverage of IPTp and antenatal care attendance. Eligible participants were women of reproductive age who had ended a pregnancy in the 12 months preceding the interview and who had resided in the selected household during at least the past 4 months of pregnancy. Coverage was calculated using percentages and 95% confidence intervals. Results A total of 3911 women were interviewed from March to October 2018. Coverage of at least three doses of IPTp (IPTp3+) was 22% and 24% in DRC project districts; 23% and 12% in Madagascar districts; 11% and 16% in Nigeria local government areas; and 63% and 34% in Mozambique districts. In DRC, Madagascar and Nigeria, more than two-thirds of women attending at least four antenatal care visits during pregnancy received less than three doses of IPTp. Conclusions The IPTp3+ uptake in the survey districts was far from the universal coverage. However, one of the study districts in Mozambique showed a much higher coverage of IPTp3+ than the other areas, which was also higher than the 2018 average national coverage of 41%. The reasons for the high IPTp3+ coverage in this Mozambican district are unclear and require further study.

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